Nuclear targeting by means of bacterial proteins

Abstract

A nuclear delivery construct comprises (i) protein H or a fragment or derivative thereof that is capable of being targeted to the nucleus of a eukaryotic cell; and associated therewith (ii) one or more other components whose targeting to the nucleus of the eukaryotic cell is desired.

1. A method of targeting one or more components to the nucleus of a lymphocyte or epithelial cell, said method comprising administering a nuclear delivery construct to said lymphocyte or epithelial cell, wherein said nuclear delivery construct is comprised of:
 (i) a polypeptide comprising the sequence as set forth in SEQ ID NO: 6, amino acids 42 to 376 of SEQ ID NO: 6, amino acids 42 to 346 of SEQ ID NO: 6 or amino acids 42 to 326 of SEQ ID NO: 6; and conjugated or fused therewith; 
 (ii) said one or more components whose targeting to the nucleus of the lymphocyte or epithelial cell is desired. 
 
     
     
       2. The method of  claim 1 , wherein the construct is targeted to the nucleus of a cell in which nucleophosmin (NPM)/B23 is up-regulated. 
     
     
       3. The method of  claim 1 , wherein component (i) of said construct interacts with actin, NPM/B23, protein SET or hnRNP A2/B1. 
     
     
       4. The method of  claim 2 , wherein component (i) of said construct interacts with actin, NPM/B23, protein SET or hnRNP A2/B 1. 
     
     
       5. The method of  claim 1 , wherein the cell is a tumor cell or proliferating cell. 
     
     
       6. A method of targeting one or more components to the nucleus of a lymphocyte, said method comprising administering a nuclear delivery construct to said lymphocyte, wherein said nuclear delivery construct is comprised of:
 (i) a polypeptide comprising the sequence as set forth in SEQ ID NO: 6, amino acids 42 to 376 of SEQ ID NO: 6, amino acids 42 to 346 of SEQ ID NO: 6 or amino acids 42 to 326 of SEQ ID NO: 6; and conjugated or fused therewith; 
 (ii) said one or more components whose targeting to the nucleus of the lymphocyte is desired. 
 
     
     
       7. A method of targeting one or more components to the nucleus of a lymphocyte, said method comprising administering a nuclear delivery construct to said lymphocyte, wherein said nuclear delivery construct is comprised of:
 (i) a polypeptide comprising the sequence as set forth in SEQ ID NO: 6, amino acids 42 to 376 of SEQ ID NO: 6, amino acids 42 to 346 of SEQ ID NO: 6 or amino acids 42 to 326 of SEQ ID NO: 6; and covalently associated therewith; 
 (ii) said one or more components whose targeting to the nucleus of the lymphocyte is desired. 
 
     
     
       8. A method of targeting a single component to the nucleus of a lymphocyte, said method comprising administering a nuclear delivery construct to said lymphocyte, wherein said nuclear delivery construct is comprised of:
 (i) a polypeptide comprising the sequence as set forth in SEQ ID NO: 6, amino acids 42 to 376 of SEQ ID NO: 6, amino acids 42 to 346 of SEQ ID NO: 6 or amino acids 42 to 326 of SEQ ID NO: 6; and covalently associated therewith; 
 (ii) the component whose targeting to the nucleus of the lymphocyte cell is desired.